Drug resistance in an age-of-infection model

ABSTRACT

In the case of a disease spreading over a time-scale comparable to the average lifetime in a host population, when the infectiousness of individuals depends on the tine since the onset of infection and when infections involve both drug-sensitive and drug-resistant strains of a pathogen, resistance may develop during the treatment of drug-sensitive strains. If increasing the treatment rate reduces the reproduction number of the drug-sensitive strain to a value below the reproduction number of the drug-resistant strain, then the disease may persist at a boundary equilibrium where only drug-resistant infection is present.     

A Framework for Analyzing the Economic Tradeoffs Between Urban Commerce and Security Against Terrorism

This article presents a framework for economic consequence analysis of terrorism countermeasures. It specifies major categories of direct and indirect costs, benefits, spillover effects, and transfer payments that must be estimated in a comprehensive assessment. It develops a spreadsheet tool for data collection, storage, and refinement, as well as estimation of the various components of the necessary economic accounts. It also illustrates the usefulness of the framework in the first assessment of the tradeoffs between enhanced security and changes in commercial activity in an urban area, with explicit attention to the role of spillover effects. The article also contributes a practical user interface to the model for emergency managers.     

A Comparative Pharmacokinetic Estimate of Mercury in U.S. Infants Following Yearly Exposures to Inactivated Influenza Vaccines Containing Thimerosal

The use of thimerosal preservative in childhood vaccines has been largely eliminated over the past decade in the United States because vaccines have been reformulated in single‐dose vials that do not require preservative. An exception is the inactivated influenza vaccines, which are formulated in both multidose vials requiring preservative and preservative‐free single‐dose vials. As part of an ongoing evaluation by USFDA of the safety of biologics throughout their lifecycle, the infant body burden of mercury following scheduled exposures to thimerosal preservative in inactivated influenza vaccines in the United States was estimated and compared to the infant body burden of mercury following daily exposures to dietary methylmercury at the reference dose established by the USEPA. Body burdens were estimated using kinetic parameters derived from experiments conducted in infant monkeys that were exposed episodically to thimerosal or MeHg at identical doses. We found that the body burden of mercury (AUC) in infants (including low birth weight) over the first 4.5 years of life following yearly exposures to thimerosal was two orders of magnitude lower than that estimated for exposures to the lowest regulatory threshold for MeHg over the same time period. In addition, peak body burdens of mercury following episodic exposures to thimerosal in this worst‐case analysis did not exceed the corresponding safe body burden of mercury from methylmercury at any time, even for low‐birth‐weight infants. Our pharmacokinetic analysis supports the acknowledged safety of thimerosal when used as a preservative at current levels in certain multidose infant vaccines in the United States.     

Longitudinal relations between behavioral inhibition and social information processing: Moderating role of maternal supportive reactions to children's emotions

Utilizing multiple measures of interpretive biases, the current study examined the roles of toddlers’ behavioral inhibition (BI) and maternal supportive reactions to children's negative emotions in relation to children's interpretive biases across middle to late childhood. Toddlers’ BI was measured during several laboratory tasks (n = 248) at 2 and 3 years of age. Mothers reported on their reactions to children's negative emotional expressions when children were 7 years old (n = 203), and children's interpretations of social cues were assessed at 7 and 10 years of age (n s = 179 and 161, respectively). Toddlers with high levels of BI expressed less positivity toward social engagement with unfamiliar peers during discussion of ambiguous social situations. Further, children with high BI were less likely to attribute the cause of negative social situations to external factors, particularly when mothers were less accepting of children's negative emotional displays. Findings are discussed in terms of cognition related to the interpretation of ambiguous and threat‐related social situations among temperamentally at‐risk children.     

女性香水容器的造型设计与时代审美特点的关系

女性香水容器造型设计的历史与时代审美相一致,其造型形式随着时代发展表现出不同的类型,这些类型的变化显示了其历史的演进与各个时代审美特点之间的密切关系。     

Complex Latent Variable Modeling in Educational Assessment

Bayesian item response theory models have been widely used in different research fields. They support measuring constructs and modeling relationships between constructs, while accounting for complex test situations (e.g., complex sampling designs, missing data, heterogenous population). Advantages of this flexible modeling framework together with powerful simulation-based estimation techniques are discussed. Furthermore, it is shown how the Bayes factor can be used to test relevant hypotheses in assessment using the College Basic Academic Subjects Examination (CBASE) data.     

A Stochastic Model to Assess the Effect of Meat Inspection Practices on the Contamination of the Pig Carcasses

The objective of meat inspection is to promote animal and public health by preventing, detecting, and controlling hazards originating from animals. With the improvements of sanitary level in pig herds, the hazards profile has shifted and the inspection procedures no longer target major foodborne pathogens (i.e., not risk based). Additionally, carcass manipulations performed when searching for macroscopic lesions can lead to cross‐contamination. We therefore developed a stochastic model to quantitatively describe cross‐contamination when consecutive carcasses are submitted to classic inspection procedures. The microbial hazard used to illustrate the model was Salmonella, the data set was obtained from Brazilian slaughterhouses, and some simplifying assumptions were made. The model predicted that due to cross‐contamination during inspection, the prevalence of contaminated carcass surfaces increased from 1.2% to 95.7%, whereas the mean contamination on contaminated surfaces decreased from 1 logCFU/cm² to ?0.87 logCFU/cm², and the standard deviations decreased from 0.65 to 0.19. These results are explained by the fact that, due to carcass manipulations with hands, knives, and hooks, including the cutting of contaminated lymph nodes, Salmonella is transferred to previously uncontaminated carcasses, but in small quantities. These small quantities can easily go undetected during sampling. Sensitivity analyses gave insight into the model performance and showed that the touching and cutting of lymph nodes during inspection can be an important source of carcass contamination. The model can serve as a tool to support discussions on the modernization of pig carcass inspection.     

Incorporating Time‐Dose‐Response into Legionella Outbreak Models

A novel method was used to incorporate in vivo host–pathogen dynamics into a new robust outbreak model for legionellosis. Dose‐response and time‐dose‐response (TDR) models were generated for Legionella longbeachae exposure to mice via the intratracheal route using a maximum likelihood estimation approach. The best‐fit TDR model was then incorporated into two L. pneumophila outbreak models: an outbreak that occurred at a spa in Japan, and one that occurred in a Melbourne aquarium. The best‐fit TDR from the murine dosing study was the beta‐Poisson with exponential‐reciprocal dependency model, which had a minimized deviance of 32.9. This model was tested against other incubation distributions in the Japan outbreak, and performed consistently well, with reported deviances ranging from 32 to 35. In the case of the Melbourne outbreak, the exponential model with exponential dependency was tested against non‐time‐dependent distributions to explore the performance of the time‐dependent model with the lowest number of parameters. This model reported low minimized deviances around 8 for the Weibull, gamma, and lognormal exposure distribution cases. This work shows that the incorporation of a time factor into outbreak distributions provides models with acceptable fits that can provide insight into the in vivo dynamics of the host‐pathogen system.     

Differences in adolescents’ motivations for indirect,direct, and hybrid peer defending

Adolescents’ defending of peers who are being bullied—or peer defending—was recently found to be a heterogeneous behavioral construct. The present study investigated individual differences in adolescents’ motivations for executing these indirect, direct, and hybrid defending behaviors. In line with the literature on bullying as goal‐directed strategic behavior, we adopted a social evolution theory framework to investigate whether these peer‐defending behaviors could qualify as goal‐directed strategic prosocial behaviors. A sample of 549 Dutch adolescents (49.4% boys; M_age = 12.5 years, SD = 0.6 years) participated in this study. Their peer reported defending behaviors (including bullying behavior as a control variable) and the following behavioral motivations were assessed: (a) agentic and communal goals (self‐report), (b) prosocial and coercive social strategies (peer report), and (c) altruistic and egocentric motivations for prosocial behavior (self‐report). The outcomes of hierarchical linear regression analyses suggest that adolescents’ motivations for executing the different subtypes of peer defending partially overlap but are also different. While indirect defending was fostered by genuine concerns for victims’ well‐being, direct defending was more motivated by personal gains. Hybrid defending combined favorable aspects of both indirect and direct defending as a goal‐directed, strategic, and altruistically motivated prosocial behavior. The implications of these findings are discussed.     

Modeling the Adenoma and Serrated Pathway to Colorectal CAncer (ASCCA)

Several colorectal cancer (CRC) screening models have been developed describing the progression of adenomas to CRC. Currently, there is increasing evidence that serrated lesions can also develop into CRC. It is not clear whether screening tests have the same test characteristics for serrated lesions as for adenomas, but lower sensitivities have been suggested. Models that ignore this type of colorectal lesions may provide overly optimistic predictions of the screen‐induced reduction in CRC incidence. To address this issue, we have developed the Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model that includes the adenoma‐carcinoma pathway and the serrated pathway to CRC as well as characteristics of colorectal lesions. The model structure and the calibration procedure are described in detail. Calibration resulted in 19 parameter sets for the adenoma‐carcinoma pathway and 13 for the serrated pathway that match the age‐ and sex‐specific adenoma and serrated lesion prevalence in the COlonoscopy versus COlonography Screening (COCOS) trial, Dutch CRC incidence and mortality rates, and a number of other intermediate outcomes concerning characteristics of colorectal lesions. As an example, we simulated outcomes for a biennial fecal immunochemical test screening program and a hypothetical one‐time colonoscopy screening program. Inclusion of the serrated pathway influenced the predicted effectiveness of screening when serrated lesions are associated with lower screening test sensitivity or when they are not removed. To our knowledge, this is the first model that explicitly includes the serrated pathway and characteristics of colorectal lesions. It is suitable for the evaluation of the (cost)effectiveness of potential screening strategies for CRC.